Significance H. pylori infects half the world's population and is associated with the development of peptic ulcer disease and gastric cancer. Infection occurs during childhood, and prevention of infection is presumed to prevent the complications that occur later in life. Since only primates are naturally infected with H. pylori, rhesus monkeys provide an excellent model in which to evaluate a vaccine. Objectives The purpose of this study was to evaluate the efficacy in preventing experimental H. pylori infection of a recombinant vaccine mixed with one of two different adjuvants. Results Eleven rhesus monkeys raised in the nursery from birth were documented by endoscopy, serology, and urea breath test to be free of infection with H. pylori. Animals were vaccinated 4 times over 12 weeks with recombinant urease, an immunodominant antigen that is made by all strains of H. pylori, combined with either a peptidoglycolipid (N=5) or E. coli labile toxin as an adjuvant. Two animals were sham vaccinated. One week after vaccination the animals were inoculated with rhesus-derived H. pylori. Three weeks later the animals underwent endoscopy with quantitative cultures of gastric biopsies. Ten weeks after vaccination the animals were sacrificed and the entire stomach was examined quantitatively for H. pylori. Serologic response to vaccination was also assessed. All 11 monkeys were infected with H. pylori at 3 weeks and at 10 weeks after H. pylori challenge and there were no significant differences in quantitative colony counts of H. pylori. Vaccinated animals seroc onverted to H. pylori. Future Directions Effective vaccination against H. pylori may require different antigens and more effective adjuvants, or may require combinations of antigens. KEY WORDS gastric cancer, peptic ulcer disease, gastritis FUNDING NIH Grant DK51776